The larval sea lamprey is known to recover coordinated swimming following spinal cord transection. We have shown that this recovery involves a regenerative process in the spinal cord. However, current evidence suggests that point to long axon tract regeneration probably does not occur. We will try to determine more definitely whether this is so, and if so by what mechanisms behavioral recovery takes place. Animals which have been allowed to recover either free swimming or restrained in glass tubes will be studied behaviorally, physiologically, and morphologically to see whether appropriate neuronal connections are formed spontaneously, or whether they require reinforcement by behavioral molding. Intracellular injections of horseradish peroxidase and procion brown into "giant axons" and identified neurons, combined with light and electron microscopy will be carried out in order to demonstrate the distance of axonal regeneration, the degree of branching, the types of synapses formed and the types of neurons contacted. Pairs of identified neurons with known synaptic connections in normal animals, will be tested following behavioral recovery for re-established synaptic connections, either direct or polysynaptic, when they are separated by a transection. The specificities of any such connections will be evaluated by similarly determining whether synaptic connections develop between neurons which are known not to be synaptically linked ordinarily. The effect of spinal transection will be studied on the potency of pre-existing synaptic contacts between neurons on the same side of a transection. Finally, pilot studies are planned on the effect of nerve growth factor on the various parameters of regeneration. These studies will lead to further attempts to modify regeneration pharmacologically, to testing adult lampreys for regenerative potential and to application of the principles discovered to the problems of regeneration in higher vertebrates.